Gobbi M, Frittoli E, Mennini T
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Naunyn Schmiedebergs Arch Pharmacol. 1990 Oct;342(4):382-6. doi: 10.1007/BF00169453.
The present study aimed at relating the presynaptic alpha 2-adrenoceptors, known to modulate noradrenaline and serotonin release, with the recently described alpha 2A- and alpha 2B-adrenoceptor subtypes. The effects of the agonist oxymetazoline (selective for alpha 2A subtype) and of three adrenoceptor antagonists (idazoxan, 1-(2-pyrimidinyl)piperazine (PmP) and prazosin, the last one known to be alpha 2B selective) were evaluated on [3H]noradrenaline and [3H]serotonin release in superfused synaptosomes from rat brain cortex. These drugs were also tested in [3H]yohimbine binding to human platelet membranes (containing only alpha 2A receptors) and to neonatal rat lung membranes (containing only alpha 2B receptors). The affinity pattern of these compounds at alpha 2A-adrenoceptors in binding studies was oxymetazoline greater than = idazoxan greater than PmP greater than prazosin; at alpha 2B-adrenoceptors it was idazoxan greater than = prazosin greater than PmP = oxymetazoline. Oxymetazoline inhibited with high and similar potencies the K(+)-evoked [3H]noradrenaline and [3H]serotonin release, IC50 18 and 7 nM, respectively; in the same conditions, the IC50 values of noradrenaline were 42 and 168 nM, respectively. The antagonist affinity pattern (antagonism against noradrenaline) was idazoxan greater than PmP greater than prazosin, either on [3H]serotonin release. These results indicate that presynaptic alpha 2 auto- or heteroreceptors do not belong to the alpha 2B subtype and suggest that the modulation of noradrenaline and serotonin release may be mediated by the alpha 2A-adrenoceptor subtype.
本研究旨在将已知可调节去甲肾上腺素和5-羟色胺释放的突触前α2-肾上腺素能受体与最近描述的α2A-和α2B-肾上腺素能受体亚型联系起来。评估了激动剂羟甲唑啉（对α2A亚型有选择性）和三种肾上腺素能受体拮抗剂（咪唑克生、1-(2-嘧啶基)哌嗪(PmP)和哌唑嗪，已知最后一种对α2B有选择性）对大鼠脑皮质灌流突触体中[3H]去甲肾上腺素和[3H]5-羟色胺释放的影响。这些药物还在[3H]育亨宾与人血小板膜（仅含α2A受体）和新生大鼠肺膜（仅含α2B受体）的结合实验中进行了测试。在结合研究中，这些化合物对α2A-肾上腺素能受体的亲和力模式为羟甲唑啉≥咪唑克生＞PmP＞哌唑嗪；对α2B-肾上腺素能受体的亲和力模式为咪唑克生≥哌唑嗪＞PmP = 羟甲唑啉。羟甲唑啉以高且相似的效力抑制K(+)诱发的[3H]去甲肾上腺素和[3H]5-羟色胺释放，IC50分别为18和7 nM；在相同条件下，去甲肾上腺素的IC50值分别为42和168 nM。拮抗剂亲和力模式（对去甲肾上腺素的拮抗作用）为咪唑克生＞PmP＞哌唑嗪，对[3H]5-羟色胺释放的影响也是如此。这些结果表明突触前α2自身或异受体不属于α2B亚型，并提示去甲肾上腺素和5-羟色胺释放的调节可能由α2A-肾上腺素能受体亚型介导。
